Abstract Nicotine addiction is believed to be a major impediment for many people in quitting smoking, but measures of nicotine dependence such as the Heaviness of Smoking Index (HSI) have had mixed success in predicting cessation. Using the National Population Health Survey, the relationship between HSI at baseline in cycle 2 (1996–1997) and successful smoking cessation at cycle 3 (1998–1999) and cycle 4 (2000–2001) was examined in 2938 Canadian adult smokers. A logistic regression model was developed for HSI as a predictor of smoking cessation, and then tested for interaction and confounding. The odds ratio of not smoking in cycle 3 was 2.08 (95% CI: 1.51, 2.86; p < 0.001) for low HSI (< 2) compared to medium HSI. When the period of follow-up was extended, individuals with both high (> 4) HSI scores (OR 2.16; 95% CI: 1.11, 4.21; p = 0.02) and low scores (OR 2.22; 95% CI: 1.41, 3.49) had higher odds of not smoking at both cycle 3 and cycle 4 than those with medium HSI scores. The likelihood of reporting cessation was higher than expected in the Canadian population among highly dependent smokers, particularly among older smokers, those with middle or greater income adequacy, and those with no intention to quit smoking. There were no substantial changes to the results when those lost-to-follow-up were treated as continuing smokers. These findings indicate that nicotine dependence is only one factor in succeeding at a quit attempt. Individual and population strategies for smoking cessation may need to consider other influences such as cognitive, affective and environmental factors.